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51.
AJOY BASAK FRANCOIS JEAN NABIL G. SEIDAH CLAUDE LAZURE 《Chemical biology & drug design》1994,44(3):253-261
Prohormone convertase-1 (PC1) and furin are subtilisin-like endopeptidases involved in the biosynthesis of peptide hormones. Five decapeptides representing the junction between the pro-region and the catalytic region of PC1 were prepared. The core sequence corresponded to D-Tyr-Arg-Ser-Lys-Arg-Xaa-Val-Gln-Lys-Asp where D-Tyr replaces the native Glu residue and Xaa, representing the P1′ position, corresponds to L-Ser, L-Leu or the unnatural amino acids, D-Ser, β-Ala, γ-Abu, β-Cha or γ-Hyp. Another analog incorporating an Orn residue in place of the Arg at the P1 site was also prepared. These peptides, synthesized by solid-phase Fmoc chemistry, were fully characterized by FAB-MS, 1H-NMR and amino acid composition. Except for Orn, γ-Hyp, L/D-Ser and L-Leu containing analogs, the others were found to be moderate to potent competitive inhibitors of hPCl activity in the following order: γ-Abu>β-Cha>β-Ala, with Ki values ranging from 1 to 8.6 μM. Both L-Ser and L-Leu analogs were correctly cleaved at the acyl carbon COOH-terminal to the Lys-Arg pair by human PCl, whereas β-Cha, γ-Abu, β-Ala and D-Ser analogs proved to be very poor substrates. The Orn and γ-Hyp derivatives were not cleaved by the enzyme at all. The three analogs containing β-Cha, γ-Abu and β-Ala also proved to be potent inhibitors of the human furin activity in the following order: β-Ala>β-Cha> γ-Abu, with K1 ranging from 0.8 to 2.2μM. Two more peptides, modified at the P1 position by addition of a semicarbazone (SC) moiety, were also synthesized by liquid-phase chemistry. These peptides, Arg-Ser-Lys-argininal-SC and Arg-Lys-Lys-argininal-SC, also proved to be potent competitive inhibitors of hPCl and exhibited Ki values 3.6 and 2.3 μM, respectively. 相似文献
52.
Circulating endothelial cell/leucocyte adhesion molecules in ischaemic heart disease 总被引:6,自引:0,他引:6
ANDREW D. BLANN JEAN AMIRAL & CHARLES N. MCCOLLUM 《British journal of haematology》1996,95(2):263-265
Increased levels of the endothelial markers soluble E-selectin ( P = 0.011), soluble thrombomodulin ( P = 0.0001) and von Willebrand factor (VWF, P < 0.0001) were found in 116 patients with ischaemic heart disease compared to an equal number of age- and sex-matched asymptomatic controls. In a multivariate analysis of the markers versus the major risk factors for atherosclerosis, VWF correlated with total cholesterol ( P = 0.002) and E-selectin with sex (lower in women, P = 0.004) and triglycerides ( P = 0.007). The data point to profound differences in the release mechanisms of these three endothelial cell products and suggests that further studies into the roles of these molecules in coronary artery disease are warranted. 相似文献
53.
MARY JEAN VICKERS RN MS 《Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG》1993,22(1):17-23
Obesity is a complex health problem and, because of the incidence of obesity in women, a common concern for providers of women's health care. For many women, obesity becomes an obsession that leads to physiologic, psychologic, and social problems. To address the needs of the obese client better, nurses must acquire a comprehensive, research-based understanding of obesity. To develop a nursing care plan, the nurse must assess the client's diet history, level of motivation to effect a change in life-style, self-image, and self-esteem. 相似文献
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56.
JEAN LOUIS MEGNIEN ALAIN SIMON ANTONIA ANDRIANI PATRICK SEGOND SOPHIE JEANNIN & JAIME LEVENSON 《British journal of clinical pharmacology》1996,42(2):187-193
1 We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia.
2 Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state.
3 Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and placebo in 15 others.
4 The significant decrease ( P <0.01) in diameter induced by wrist occlusion before (0.34±0.08 mm) placebo and pravastatin (0.39±0.10 mm) persisted after placebo (0.26±0.07 mm) but was abolished after pravastatin (0.07±0.05 mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin ( P <0.01) and lower after pravastin than after placebo ( P <0.05). Diameter during wrist occlusion was higher after pravastatin than after placebo (4.35±0.16 vs 3.89±0.09 mm); P <0.01).
5 These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol. 相似文献
2 Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state.
3 Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and placebo in 15 others.
4 The significant decrease ( P <0.01) in diameter induced by wrist occlusion before (0.34±0.08 mm) placebo and pravastatin (0.39±0.10 mm) persisted after placebo (0.26±0.07 mm) but was abolished after pravastatin (0.07±0.05 mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin ( P <0.01) and lower after pravastin than after placebo ( P <0.05). Diameter during wrist occlusion was higher after pravastatin than after placebo (4.35±0.16 vs 3.89±0.09 mm); P <0.01).
5 These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol. 相似文献
57.
The Morphological Identity of Maternal Cells in Newborn Mice 总被引:3,自引:0,他引:3
The placenta has been considered ananatomical barrier which prevents maternal rejection of the fetal allograft. Thisview is no longer tenable since, in oneparticular inbred strain of mouse, maternal blood cells have been identified bymeans of radioisotope labels in newbornmice. Both maternal red cells and lymphocytes labeled, respectively, with radiochromium and tritiated thymidinehave been detected in newborn mice.This phenomenon appears independentof the trauma of normal delivery and,what is more, occurs before term. Submitted on February 17, 1970 Revised on April 29, 1970 Accepted on May 18, 1970 相似文献
58.
Proteins from secretions or homogenates of mice seminal vesicles were analysed by polyacrylamide gel electrophoresis. In homogenates about 15 bands were differentially induced with molecular weights (MW's) of 12, 13, 14, 15, 15.5, 71, 120 and 140 kD, or repressed molecular weights of 12.5, 14.3, 28, 30, 53, 73, 90-105 kD). The effects of castration were reversed by testosterone and dihydrotestosterone but not by oestradiol, progesterone or corticosterone. When the androgen-dependence of proteins was investigated using radioactive methionine the protein spectra showed that about 12 bands with molecular weights of 13, 13.7, 14, 15, 15.5, 16, 20.5, 24, 37, 38.5, 56, 68, 96 and 180 kD were differentially induced or repressed by androgens. Of the induced proteins, those with low molecular weight (12-15.5 kD) were accumulated in significant amounts between 20 days and 30 days, coincident with the pubertal increase of androgens in the seminal vesicles. Those induced proteins with high molecular weight (71, 120 and 140 kD) appeared between 40 days and 60 days. The androgen-repressed proteins were strongly evident in immature males, but disappeared after day 40. 相似文献
59.
Repeaed plasma exchange was used in the treatment of a 70-yr-oldman with Wegner's granulomatosis. Two days following the lastexchange, the plasma cholinesterase was 14% of normal and therewas a prolonged response to the action of suxamethonium. 相似文献
60.
GILLES MAUDUIT RAMON FERNANDEZ-BUSSY JEAN THIVOLET 《Clinical and experimental dermatology》1984,9(3):256-262
Peripheral blood T lymphocytes and T cell subsets were examined in fifteen patients with lichen planus prior to and for 4 months during treatment. The percentages of different T cell sub-populations were defined by indirect immunofluorescence using monoclonal antibodies OKT3, OKT4 and OKT8. These are specific markers of total T cells, helper-inducer T cells and suppressor-cytotoxic T cells respectively. Decreased percentages of suppressor T cells and elevated helper suppressor ratios were observed before treatment and after 1 month of therapy. These changes had disappeared by the second month of treatment, by which time all the lesions had healed. 相似文献